tbuckley/cabot-search huggingface dataset:
The IMPACT of an interdisciplinary goals-of-care program on readmission rates at a comprehensive care center.
Authors: Cerena Leung, Clark R. Andersen, Kaycee Wilson, Nico Nortje, Marina C. George, Christopher Flowers, Eduardo Bruera, David Hui
Journal: Journal of Clinical Oncology (2023)

6565 Background: Unplanned readmissions are associated with substantial distress for patients and their families. We hypothesized that goals-of-care (GOC) discussions, by improving goal-concordant care, may reduce unplanned readmissions. However, only a handful of studies have specifically examined this question. We assessed the implementation of a system-wide multicomponent interdisciplinary GOC (myGOC) program on the 30-day unplanned readmission rate and other hospital outcomes for medical patients at our comprehensive cancer center. Methods: In this retrospective cohort study, we compared the 30-day unplanned readmission rates in consecutive medical patients during the pre-implementation period from May 1, 2019 to December 31, 2019 and the post-implementation period from May 1, 2020 to December 31, 2020. The primary outcome was the 30-day unplanned readmission rate as defined by Vizient. Secondary outcomes included 7-day unplanned readmission rates, inpatient do-not-resuscitate (DNR) orders and supportive care consults. A multi-variate analysis model was used to examine the association between 30-day unplanned readmission rates and the implementation of the myGOC program adjusting for age, sex, race, index hospitalization type, and Sequential Organ Failure Assessment (SOFA) score. Results: This study included 7028 and 5982 unique medical patients during the pre- and post-implementation period, respectively. The 30-day unplanned readmission rates decreased from 13.7% before to 12.0% after implementation of the myGOC program. After adjusting for covariates, the myGOC implementation remained significantly associated with a reduction in 30-day unplanned readmission rates (OR [95% CI] 0.85 [0.77, 0.95], p=0.003). Other factors significantly associated with a decreased likelihood of a 30-day unplanned readmission were hematologic malignancies (vs. solid: 0.71 [0.64, 0.79]), White race (vs. Hispanic: 0.86 [0.75, 0.98]), an inpatient DNR order (0.30 [0.25, 0.37], an ICU admission (0.58 [0.48, 0.71], and an emergent admission (vs. elective: 0.86 [0.76, 0.99]). We also observed a significant decrease in 7-day unplanned readmission rates (0.75 [0.64, 0.89], p=0.0009), an increase in inpatient DNR orders (1.48 [1.35, 1.63], p&lt;0.0001) and an increase in supportive care consults (1.22 [1.13, 1.31], p&lt;0.0001) post-implementation. Conclusions: Implementation of a system-wide multicomponent GOC intervention was associated with a significant reduction in 30-day unplanned readmission rates after accounting for other key clinical factors.
The utilization of lenvatinib with pembrolizumab for the treatment of recurrent endometrial cancer.
Authors: Mali Barbi, Chung-Shien Lee, Husneara Rahman, Kit Cheng, Lee Jean, Veena S. John
Journal: Journal of Clinical Oncology (2023)

e17627 Background: The landscape for the treatment of microsatellite-stable-recurrent endometrial cancer has changed with the published results of the KEYNOTE-775, demonstrating an overall response rate of 37.2% with Pembrolizumab and Lenvatinib 20 mg. However, recent retrospective studies have suggested that a lower dose of Lenvatinib may be safer and equally efficacious. We aimed to retrospectively review our institutional data to compare the efficacy and toxicity of Lenvatinib at a low (≤10 mg) vs. high (&gt;10 mg) dose. Methods: Retrospective review of patients with recurrent endometrial cancer who received ≥ 3 cycles of Pembrolizumab with Lenvatinib. A Univariate analysis was used to estimate the 1-year progression-free survival (PFS) and overall survival (OS), and a Multivariate Cox PH regression model was used to estimate the hazard ratio (HR) with a 95% confidence interval (CI) and p&lt;0.05. Results: 77 patients were included in this analysis, the median age and BMI were 70 years and 28.5 kg/m2, respectively (Table 1). Most tumors were PDL-1&lt;1% (67.2%) and were microsatellite stable (95%). 4 patients had MSI-H. Most patients started at a lower dose (66%, median of 10 mg), and 34% of patients started at a higher dose (n=26, median of 14 mg). The most common dose was 10 mg (41%, n=32) and 13% of patients received 20 mg (n=10). In the lower dose group, 71% had ECOG 0-1 vs. 77% in the higher dose, and were more likely to have &gt; 2 lines of treatment (45% vs. 22%). The median time to interruption was 41 vs. 51 days respectively. The PFS and OS were not statically different (Table 1). Multivariate analysis showed a significantly higher HR in the lower dose group (2.5 [CI 1.12-5.56], p=0.025). Conclusions: TheFDA-recommended dose of Lenvatinib of 20 mg is perceived to be difficult to tolerate and patients are often started on a lower dose. In this study, we observed that the time to interruption was longer in the higher dose than in the lower dose group. Though we failed to detect a significant differences in PFS/OS, when adjusted for age, we observed a significantly higher HR of progression or death in the lower dose group. Possible explanations for our observations are that patients who received a lower dose were older and frailer. Our findings call to question the common practice of starting Lenvatinib at a low dose. Further analysis is warranted to delineate the required dose that is both efficacious and safe. [Table: see text]
The clinical efficacy and safety of sintilimab plus anlotinib for unresectable intrahepatic cholangiocarcinoma (ICC): A prospective, single-arm phase II study.
Authors: Jian-Wen Cheng, Xin-Rong Yang, Yang Xu, Xiao-Wu Huang, Shuang-Jian Qiu, Hui-Chuan Sun, Jia Fan, Jian Zhou
Journal: Journal of Clinical Oncology (2023)

e16170 Background: Intrahepatic cholangiocarcinoma (ICC) is the second-most common primary liver malignancy. Immunotherapy plus chemotherapy regimen (such as TOP-AZ study) had demonstrated important therapeutic advantages in ICC, but the severe AEs reaction to chemotherapy might deteriorate treatment compliance, performance status and quality of life, and even subsequent treatment eligibility. Hence there is an unmet need for a more tolerable regimen with comparable efficacy for patients with unresectable ICC. The clinical benefits of combining Sintilimab and Anlotinib have been reported in a variety of clinical studies of solid tumors, such as non-small cell lung cancer and hepatocellular carcinoma. This trial aims to explore the safety and efficacy of Sintilimab plus Anlotinib in unresectable ICC. Methods: This is a prospective, single-arm, open-label exploratory, phase II study (ChiCTR2000035901). Eligible unresectable ICC patients received Sintilimab (200 mg, iv, d1) and Anlotinib (12 mg, po, d1-14) every 3 weeks till disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR) assessed by RECIST v1.1 and secondary endpoints included progression-free survival (PFS), disease control rate (DCR), duration of response (DOR), overall survival (OS), surgical conversion rate, as well as safety and tolerability. Results: Up to the end of January 2023, 18 patients were enrolled with a median age of 60.4 years (range 36-73), 61.1% were male, and all patients were classified into Child-Pugh A. 12 of 18 patients (66.7%) presented with TNM stage IV and 8 (8/18, 44.4%) patients had distant metastasis. All patients were efficacy evaluable, confirmed ORR was 33.3% and DCR was 83.3%. Of these, 16.7% (3/18) patients achieved complete response (CR), and 16.7% (3/18) patients achieved partial response (PR). Median PFS was 7.49 months (95% CI: 3.12-13.2). Among those, 3 (16.7%) patients further received surgical resection and 2 of 3 them were still disease-free survival till last follow-up. Treatment-related AEs (TRAEs) occurred in 12/18 pts (66.7%), while the most commonly reported TRAEs were hypertension in 29.6%. Grade 3 TRAEs occurred in 6/18 pts (33.3%) and there was no grade 4-5 TRAEs. Conclusions: In view of its encouraging efficacy and safety profile, Sintilimab plus Anlotinib might represents a viable and safe chemotherapy-free regimen in unresectable ICC treatment. Enrollment and further follow-up are ongoing. Clinical trial information: ChiCTR2000035901 .
Molecular diagnostic classification for cancers of unknown primary (CUP): Post-testing diagnosis and treatment impact analysis from real-world claims data.
Authors: Zachary Rivers, Ryan W Huey, Rotem Ben-Shachar, Anjali Narayan Avadhani, Timothy J. Taxter, Kyle A. Beauchamp, Adam J Hockenberry, Halla Nimeiri, Joelle Allam, Aparna Kalyan, Kanwal Pratap Singh Raghav, Michael Sangmin Lee
Journal: Journal of Clinical Oncology (2023)

6610 Background: Next-generation sequencing-based molecular diagnostic classifiers can help identify the tissue of origin for CUP, and enable the selection of site-specific therapies (as opposed to empiric chemotherapy) for this vulnerable population with high unmet need. NCCN guidelines do not endorse the use of tissue of origin classifiers as standard of care for CUP patients due to limited clinical evidence. Here, we linked results of a commercial molecular diagnostic classifier with claims data to understand how this test impacted patient care. Methods: We assessed de-identified claims data from the Komodo Healthcare Map (a database including provider visits, laboratory tests, procedures, imaging, and prescriptions) linked to the Tempus Tumor Origin (TO) test—a machine learning classifier that uses RNA-seq data to classify tumors into one of 68 histological subtypes. Eligible patients had pathologist-confirmed CUP and were classified as one of 9 subtypes (each having n&gt;10). Impact was determined by identifying either one or more new diagnostic codes or new subtype-related medication claims following TO testing. Results: We analyzed data from 490 patients: 483 for the diagnosis analysis and 213 for the medication analysis (206 patients appear in both, due to differences in timing of diagnosis vs. medication claims). We found that post-TO testing, 49.9% (n=241) of patients had a diagnostic code change, 63.8% (n=136) had a treatment change, and 41% (n=85) had both. In total, 59.6% (n=292) of patients were impacted by the use of this classifier, with variation according to predicted subtype (Table). Cancer types with specific treatment options were more likely to have changes in diagnostic code or treatment. For CUP predicted as lung adenocarcinomas, 85% of the cases had a new subtype-aligned medication, and 78% were specifically placed on immunotherapy (IO) compared with 24% of overall patients. Conclusions: Using real-world claims data, we show that molecular diagnostic testing utilizing Tempus TO impacted care for a majority of CUP patients. This cohort will be followed to identify how TO testing decisions impact outcomes. [Table: see text]
Final three-year follow-up analysis of phase I/II study on tirabrutinib in patients with relapsed or refractory primary central nervous system lymphoma.
Authors: Katsunori Asai, Yoshitaka Narita, Motoo Nagane, Kazuhiko Mishima, Yasuhito Terui, Yoshiki Arakawa, Hajime Yonezawa, Noriko Fukuhara, Kazuhiko Sugiyama, Naoki Shinojima, Arata Aoi, Ryo Nishikawa
Journal: Journal of Clinical Oncology (2023)

7548 Background: Primary central nervous system lymphoma (PCNSL) is known as an uncommon and extremely aggressive type of non-Hodgkin lymphoma of brain tumors. Tirabrutinib (TIR), a second-generation oral Bruton’s tyrosine kinase inhibitor, was approved for the treatment of relapsed or refractory PCNSL (rrPCNSL) based on the results of phase I/II study in Japan (Trial registration: JapicCTI-173646) in 2020. Methods: In this study, 44 Japanese patients with rrPCNSL received TIR QD at doses of 320 mg (n = 20), 480 mg (n = 7), or 480 mg while fasting (480 mg fasted: n = 17). The International PCNSL Collaborative Group criteria were used to assess the primary endpoint, which was the overall response rate (ORR). We previously reported the interim results with 14.9 (range:1.4–27.7) months of median follow-up in 2020 (Mishima et al., the 25th Society for Neuro-Oncology 2020). The final analysis results with a three-year follow-up are reported here (data cutoff: April 27 th , 2022). Results: For the entire population, the ORR was 63.6% with 36.4% of complete response, the median duration of response was 9.2 months, the median progression-free survival was 2.9 months, and the median overall survival was not reached (median follow-up: 37.1 months). The most frequent adverse events (AEs) were skin and subcutaneous tissue disorders and blood and lymphatic system disorders at any grade, including rash (36.4%) and neutropenia (27.3%), leukopenia (25.0%), lymphopenia (18.2%), and thrombocytopenia (11.4%). Grade ≥3 AEs were neutropenia (9.1%), leukopenia (9.1%), lymphopenia (6.8%), and erythema multiforme (6.8%). One patient with 480 mg had grade 5 AEs (Pneumocystis jirovecii pneumonia and Interstitial lung disease), while neither new grade 5 AEs nor new safety profiles were observed since the last data cutoff. As of the current data cutoff, 15 and 6 of 44 patients had been receiving TIR for more than one and three years, respectively, and 5 of the 6 patients continued receiving TIR, including 4 patients who were receiving 480 mg fasted. Conclusions: In conclusion, TIR showed long-lasting effectiveness in a subset of patients with a tolerable safety profile of rrPCNSL. Clinical trial information: JapicCTI-173646. [Table: see text]
Characterizing progression to subsequent lines of therapy in metastatic renal cell carcinoma (mRCC) after nivolumab plus ipilimumab (Nivo+Ipi): Results from the International mRCC Database Consortium (IMDC).
Authors: Audreylie Lemelin, Kosuke Takemura, Matthew Scott Ernst, J Connor Wells, Frede Donskov, Camillo Porta, Guillermo de Velasco, Ian D. Davis, Lori Wood, Sumanta Kumar Pal, Aaron Richard Hansen, Christian K. Kollmannsberger, Georg A. Bjarnason, Ben Tran, Haoran Li, Ravindran Kanesvaran, Thomas Powles, Rana R. McKay, Toni K. Choueiri, Daniel Yick Chin Heng
Journal: Journal of Clinical Oncology (2023)

4538 Background: Treatment patterns and number of lines of therapy for patients with mRCC are not well characterized in the era of immunoncology-based combinations. We aimed to quantify the attrition rates by line of therapy and to examine predictors of receiving second-line (2L) treatment. Methods: Using the IMDC, patients with mRCC who received first-line (1L) Nivo+Ipi were included. Clinical and pathologic characteristics and outcomes were extracted. Chi-square tests were used to compare categorical variables between patients who received 2L and those who did not. A logistic regression model was used to assess predictors of 2L therapy initiation in eligible patients. Results: 995 patients treated with 1L Nivo+Ipi were identified, of whom 704 stopped 1L and were thus eligible for 2L therapy. Reasons for stopping 1L included progressive disease (PD) in 39.5%, toxicity in 25.0%, death in 4.3%, complete response in 1.6% and other in 29.7%. Among 2L eligible patients, 410 (58.2%) received 2L whereas 294 (41.8%) did not. Patients who stopped 1L for PD were more likely to initiate 2L than those who stopped for other reasons (81.7% vs 43.0%, p &lt;0.001). Patients who received 2L were more likely to have clear-cell histology (75.1 vs 62.9%, p=0.02), bone metastases (39.8 vs 29.6%, p=0.01), and only one site of metastases (18.3 vs 10.5%, p=0.01) and less likely to be poor risk by IMDC criteria (27.1 vs 34.4%, p=0.03). After adjusting for IMDC criteria, no predictors of receiving 2L therapy remained significant. The overall response rate to 1L therapy was lower in patients who received 2L than in those who did not: 18.5% (76/366) and 33.7% (99/245), respectively (p&lt;0.001). Among 258 patients who stopped 2L, 145 (56.2%, overall 20.6%) started third-line (3L) therapy. Of the 98 patients who stopped 3L, 52 (53.1%, overall 7.4%) started fourth-line therapy. Conclusions: In our study, we found that over half of eligible patients received the subsequent line of therapy. We were unable to identify predictors of 2L therapy initiation. Attrition rates between lines of therapy have important implications for patient counseling, cost analyses, and clinical trial design. [Table: see text]
Randomised phase III trial of the hypoxia modifier nimorazole added to radiotherapy with benefit assessed in hypoxic head and neck cancers determined using a gene signature (NIMRAD).
Authors: David Thomson, Nick Slevin, Helen Baines, Guy Betts, Steve Bolton, Mererid Evans, Kate Garcez, Joely Irlam, Lip Lee, Nicola Melillo, Hitesh Mistry, Elisabet More, Christopher Nutting, James Price, David Ryder, Stefano Schipani, Mehmet Sen, Huiqi Yang, Catharine West
Journal: Journal of Clinical Oncology (2023)

6006 Background: Tumour hypoxia is an adverse prognostic factor in head and neck squamous cell carcinoma (HNSCC). We assessed whether patients with hypoxic HNSCC benefited from the addition of nimorazole to definitive radiotherapy (RT). Methods: NIMRAD was a phase III, multi-centre, placebo-controlled, double-blind trial in patients with HNSCC unsuitable for concurrent platinum chemotherapy or cetuximab with definitive RT (NCT01950689). Patients were randomized 1:1 to receive nimorazole (1.2 g/m 2 daily, prior to RT) + RT (65 Gy in 30 fractions over 6 weeks) or placebo (taken via the same schedule) + RT. The primary endpoint was loco-regional control (freedom from loco-regional progression, FFLRP) in patients with hypoxic tumours, defined as greater than or equal to the median hypoxia score of the first 50 patients analysed (≥0.079), using a validated 26-gene signature. The planned sample size was 340 patients allowing for signature generation in 85%, assumed HR 0.50 for nimorazole effectiveness in the hypoxic group, and requiring 66 loco-regional failures to have 80% power in a two-tail log-rank test at the 5% significance level. Results: 338 patients were randomised by 19 UK centres from May 2014 to May 2019, with a median follow-up of 3.1 years (95%CI 2.9-3.4). Hypoxia scores were available for 286 (85%). The median patient age was 73 years (range 44-88); and clinical factors were balanced between the arms, both for the whole population and hypoxic group (Table). There were 36 (25.9%) loco-regional failures in the hypoxic group, where nimorazole + RT did not improve FFLRP (adjusted HR 0.72; 95% CI 0.36-1.44; p=0.35), or overall survival (adjusted HR 0.96; 0.53-1.72; p=0.88) compared with placebo + RT. Similarly, nimorazole + RT did not improve FFLRP or OS in the whole population. In total (n=338), 73% of patients allocated nimorazole adhered to the drug for ≥50% of RT fractions. Nimorazole + RT caused more acute nausea compared with placebo + RT (CTCAE v4.0 G1+2: 56.6% vs 42.4%, G3: 10.1% vs 5.3%, respectively; p=0.003), with no differences in other early or late toxicities. Conclusions: Addition of the hypoxia modifier nimorazole to RT for locally advanced HNSCC in older and less fit patients did not improve loco-regional control or survival. Clinical trial information: NCT01950689 . [Table: see text]
Single-cell RNA sequencing and influences of necroptosis-associated myeloid lineages in immune microenvironment of PDAC.
Authors: Weiwei Dong, Huixia Zhao, He Zhang, Zhiyan Zeng, Yanyan Hu, Tongqiang Fan, Liuqing Zheng, Qian Wang, Shanshan Xiao, Tao Wang, Wenhua Xiao
Journal: Journal of Clinical Oncology (2023)

e16261 Background: Tumor-infiltrating myeloid cells (TIMs) are abundant in tumor stroma and emerging evidence indicate that the presence of these cells influences clinical outcomes in many cancer types. TIMs play important roles in tumor progression and specific subsets may exhibit divergent anti-tumor or tumor-promoting functions. Currently, the molecular characteristics of TIMs in pancreatic ductal adenocarcinoma (PDAC) largely remain unknown. Like other programmed cell death procedures such as ferroptosis and pyroptosis, necroptosis has recently emerged as an important cellular event that modulates tumorigenesis and tumor progression. Combination of necroptosis and TIMs is of great interest to study the molecular mechanism of clinical outcomes for PDAC patients. Methods: This study enrolled 16 PDAC patients. The scRNA-seq data were obtained from a published dataset and each patient included primary tumor, metastatic tumor, primary tumor-adjacent and PBMC samples. All myeloid cells comprising granulocytes, monocytes, macrophages, and dendritic cells from enrolled patients were extracted for further analysis. We performed comprehensive analysis about the characteristics of myeloid lineages, differentially expressed genes, pathway enrichment analysis and novel cell subtype identification. The necroptosis-associated novel TIMs cell sub-clusters were elucidated in detail. Results: To comprehensively analyze the heterogeneous TIMs microenvironment in PDAC patients using scRNA-seq dataset, we firstly obtained consistently upregulated genes among granulocytes, monocytes, macrophages, and dendritic cell types between tumor samples and non-tumor samples. Those uniquely expressed genes represent different functions in necroptosis-associated TIMs cells. In total, we identified 10 necroptosis-associated upregulated genes in PDAC tumors and 5 upregulated genes in tumor-adjacent and peripheral blood samples, respectively. Based on the cells expressed those necroptosis-related genes, we identified three novel cell populations, including GLUL - SQSTM1 - RTM, HSP90AA1 + HSP90AB1 + mast cells, and JAK3 + TLR4 + CD16 monocytes, which were regulators of immunity either tumor-promoters or tumor-suppressors. Clinical outcomes further supported their function roles in the PDAC tumor microenvironment. Conclusions: This study comprehensively studied the heterogeneity of myeloid microenvironment in PDAC by scRNA-Seq. Several necroptosis-associated genes and myeloid cell sub-clusters were identified and they have prognostic clinical values in PDAC. These preliminary results were helpful for further understanding the molecular mechanism of PDAC treatment strategies.